rs386833484

Variant names:

• chr7-107791093-C-G
• rs386833484
• NM_000111.3:c.525G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000111.3(SLC26A3):​c.525G>C​(p.Arg175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC26A3 NM_000111.3 missense
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.00
• Publications: 3 publications found

Genes affected

SLC26A3 (HGNC:3018): (solute carrier family 26 member 3) The protein encoded by this gene is a transmembrane glycoprotein that transports chloride ions across the cell membrane in exchange for bicarbonate ions. It is localized to the mucosa of the lower intestinal tract, particularly to the apical membrane of columnar epithelium and some goblet cells. The protein is essential for intestinal chloride absorption, and mutations in this gene have been associated with congenital chloride diarrhea. [provided by RefSeq, Oct 2008]

SLC26A3 Gene-Disease associations (from GenCC):

• congenital secretory chloride diarrhea 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 7-107791093-C-G is Pathogenic according to our data. Variant chr7-107791093-C-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 56003.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A3	NM_000111.3	c.525G>C	p.Arg175Ser	missense_variant	Exon 5 of 21	ENST00000340010.10	NP_000102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A3	ENST00000340010.10	c.525G>C	p.Arg175Ser	missense_variant	Exon 5 of 21	1	NM_000111.3	ENSP00000345873.5
SLC26A3	ENST00000379083.7	n.*316G>C		non_coding_transcript_exon_variant	Exon 5 of 20	2		ENSP00000368375.3
SLC26A3	ENST00000379083.7	n.*316G>C		3_prime_UTR_variant	Exon 5 of 20	2		ENSP00000368375.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital secretory diarrhea, chloride type Pathogenic:1

-

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	12
DANN	Benign	0.86
DEOGEN2	Uncertain	0.53	D
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.047	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.0
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.57
Sift	Benign	0.070	T
Sift4G	Benign	0.20	T
Polyphen		0.0010	B
Vest4		0.68
MutPred		0.60		Gain of phosphorylation at R175 (P = 0.0283);
MVP		0.78
MPC		0.19
ClinPred		0.30	T
Varity_R		0.39
gMVP		0.54
Mutation Taster		=94/6	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs386833484; hg19: chr7-107431538;